Radioactive isotopes have a variety of applications. The choice of an appropriate isotope for any particular use depends on such factors as its half life and the type and energy of the radiation produced. The usefulness of certain isotopes may, however, be severly curtailed by the difficulty of their production and isolation.
Radiation therapy has long been used in the treatment of cancer and other localized lesions. The development of monoclonal antibodies, which can be targeted to specific cells with a high degree of specificity, has made it possible to selectively deliver radioactive agents predominantly to specifically targeted cells. The choice of an appropriate radioactive isotope is the critical aspect in targeting radiation therapy. An appropriate radioactive isotope should, desirably, have a half life which is long enough to permit any necessary logistic and pharmaceutical operations (transport, reaction, sterilization, etc.) prior to administration and arrival at the targeted cell after administration, without much loss of activity and damage in route, but is short enough so that therapeutic action proceeds rapidly. Generally one also desires radiation which is highly cytotoxic at short range so that the cell to which the antibody is attached is killed (as well as immediately adjacent cells that are likely to be also pathogenic) but harmless over longer distances so as not to injure healthy surrounding tissue. Absence of harmful persistent residues is also important.
Many potential radioactive candidates require a cyclotron for production and cannot be seriously considered for regular therapeutic use because of cost and availability reason. Of those possible candidates that do not need to be produced in a cyclotron, .sup.212 Bi and .sup.212 Pb have received considerable attention because they have acceptable decay form, energy, and half life characteristics.
While methods for producing both .sup.212 Bi and .sup.212 Pb are known, most require the use of complex equipment having a rather short life span. One less complicated, long lived generator for producing both .sup.212 Bi and .sup.212 Pb is shown in the literature by Zucchini et al., Intl. J. Nucl. Med. & Bio., Vol. 9, pp. 83 to 84 (June 1982). To produce .sup.212 Pb in this generator, a bed of sodium titanate is maintained in a quartz column in which .sup.228 Th in the tetravalent state and radium-224 (.sup.224 Ra) can be adsorbed above a coarse fritted glass disk sealed in the column. When water is passed through the titanate, .sup.220 Rn, which is a decay product of .sup.224 Ra, dissolves in the water. The water containing the .sup.220 Rn passes through the fritted disk and is collected in a glass reservoir containing 2 cc of water therebelow. Since substantially all of the .sup.220 Rn decays within 5 minutes in the water to .sup.212 Pb, this provides sufficient delay. The water containing the .sup.220 Rn is passed from the reservoir into a column containing a strongly acidic ion exchange resin, such as Bio-Rad AG-50 WX18 cation exchange resin (Bio-Rad, Richmond, Calif.), which adsorbs .sup.212 Pb as the water passes through the column. After sufficient .sup.212 Pb has been absorbed, the resin column is removed and the .sup.212 Pb eluted therefrom using 2N HCl to convert the lead isotope to PbCl.sub.3. However, residual radioactivity and contamination was reported when this procedure was used, apparently due to a small amount of .sup.228 Th and .sup.224 Ra eluted. To reduce the contamination an additional ion exchange treatment is required.
There thus exists a need to provide an apparatus and method by which certain useful radioactive isotopes can be efficiently and safely produced. The present invention satisfies this need and provides related advantages as well.